The proposed two-year research project aims to develop silicon-based miniaturized high- frequency (MHz) ultrasonic nozzles capable of producing monodispersed liquid droplets 2.2 - 4.1 um and solid particles 0.4 - 2.2 um in diameter. Such micron-size particles have multiple biomedical applications including pulmonary drug delivery and preparation of drugs for inhalation. The five specific aims are: (1) to establish the optimum design methodology for high-performance nozzles operating at 1.0 up to 2.5 MHz ultrasonic frequency, (2) to establish a viable nozzle fabrication technique, (3) to determine the atomization characteristics of such ultrasonic nozzles, (4) to evaluate the deposition patterns of monodispersed droplets and particles produced, and (5) to study the feasibility of producing biopolymer particles for microencapsulation and the basic surface science involved. The five corresponding research tasks to achieve these aims are: (1) Design and simulation of multiple Fourier horns-based nozzles using a 3-D ANSYS Program, (2) Nozzle fabrication using micro-electromechanical system (MEMS) technology, (3) Atomization experiment and verification of capillary wave mechanism at target ultrasonic frequencies, and other nozzle performance characterizations, (4) Size and deposition characterizations of medicinal sprays (isoproterenol and insulin) using an established airway model, and (5) Spray drying and parametric study of biopolymer (poly- lactic acid and poly-lactic-co-glycolic acid) dispersions for microencapsulation of isoproterenol and insulin relevant to controlled release of drugs. The 0.5 MHz silicon-based 3-Fourier horn nozzles devised in the PI's group are the first to achieve 7.0 um monodispersed droplets with geometric standard deviation (GSD) as small as 1.1 by ultrasonic atomization. The novel design of multiple Fourier horns in resonance facilitates pure capillary wave atomization mechanism and, thus, yields monodispersed droplets. Proposed increase in the resonant frequency to 1.0 and 2.5 MHz should produce monodispersed liquid droplets 4.1 and 2.2 um in diameter, respectively, and the corresponding solid particles as small as 0.4 um. The proposed research will contribute significantly to the scientific advancement and technical development of high-frequency ultrasonic atomization. The miniaturized new devices have great potential to be integrated into nozzle arrays for high- throughput production of monodispersed micro- and nano-size drug particles and into efficient pocket-sized nebulizers. Therefore, they should have important implications for public health. PI: Chen S. Tsai MEMS-Based High-Frequency Ultrasonic Nozzles for Medical Applications PROJECT NARRATIVE The proposed research will contribute significantly to the scientific advancement and technical development of high-frequency ultrasonic atomization. The resulting silicon-based miniaturized megahertz ultrasonic nozzles are capable of producing micron-size monodispersed medicinal liquid droplets and solid particles for targeted delivery of reproducible doses to the respiratory system. Such new devices may ultimately be developed into efficient pocket-sized nebulizers for drug delivery by inhalation and should, therefore, have important implications for public health. [unreadable] [unreadable] [unreadable]